Combined treatment with antioxidants and immunosuppressants on cytokine release by human peripheral blood mononuclear cells - chemically injured keratocyte reaction

Mol Vis. 2011:17:2665-71. Epub 2011 Oct 15.

Abstract

Purpose: To investigate the effect of antioxidants and immunosuppresants on mixed peripheral blood mononuclear cells (PBMC) - chemically injured keratocytes reaction (MLKR).

Methods: The PBMC stimulation assay was performed using chemically injured keratocytes treated with 0.05 N NaOH for 90 s (MLKR). MLKR were treated with various drugs including rapamycin, dexamethasone, mycophenoleic acid (MPA), alpha lipoic acid (ALA), and N-acetyl cysteine (NAC). Matrix metalloprotease-9 (MMP-9), transforming growth factor-beta 1 (TGF-β1), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF) secretion profiles of activated PBMCs stimulated by NaOH-treated keratocytes were determined by ELISA.

Results: Anti-oxidants as well as immunosuppressants suppressed PBMC proliferation. MMP-9 levels were lower in antioxidants group. IL-6 levels decreased in dexamethasone group and anti-oxidants group. Combination of immunosuppressants and antioxidants suppressed more PBMC proliferation except for rapamycin + ALA group, suppressed MMP-9 production except for MPA + ALA group, decreased IL-6 levels and increased MIF levels except for rapamycin + ALA group. TGF-β1 levels were elevated in rapamycin group and rapamycin + ALA group.

Conclusions: Cytokine production was different depending on combination of drugs.Our results suggest that the different drugs should be selected for treatment according to the phases of corneal chemical burn.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Antioxidants / pharmacology*
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / immunology
  • Burns, Chemical / metabolism
  • Cells, Cultured
  • Coculture Techniques
  • Cornea / drug effects*
  • Cornea / immunology
  • Corneal Injuries
  • Corneal Keratocytes / drug effects*
  • Corneal Keratocytes / metabolism
  • Corneal Keratocytes / pathology
  • Dexamethasone / pharmacology
  • Drug Combinations
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-6 / biosynthesis
  • Intramolecular Oxidoreductases / biosynthesis
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Macrophage Migration-Inhibitory Factors / biosynthesis
  • Matrix Metalloproteinase 9 / biosynthesis
  • Mycophenolic Acid / pharmacology
  • Sirolimus / pharmacology
  • Sodium Hydroxide / adverse effects*
  • Thioctic Acid / pharmacology
  • Transforming Growth Factor beta1 / biosynthesis
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Antioxidants
  • Drug Combinations
  • Immunosuppressive Agents
  • Interleukin-6
  • Macrophage Migration-Inhibitory Factors
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Sodium Hydroxide
  • Thioctic Acid
  • Dexamethasone
  • Matrix Metalloproteinase 9
  • Intramolecular Oxidoreductases
  • MIF protein, human
  • Mycophenolic Acid
  • Sirolimus
  • Acetylcysteine